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Aging and disease    2019, Vol. 10 Issue (3) : 652-663     DOI: 10.14336/AD.2019.0118
Review |
Emerging Roles of Complement Protein C1q in Neurodegeneration
Kyoungjoo Cho*
Department of Life Science, Kyonggi University, Suwon, South Korea
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Abstract  

The innate immune system is an ancient and primary component system that rapidly reacts to defend the body against external pathogens. C1 is the initial responder of classical pathway of the innate immune system. C1 is comprised of C1q, C1r, and C1s. Among them, C1q is known to interact with diverse ligands, which can perform various functions in physiological and pathophysiological conditions. Because C1q participates in the clearance of pathogens, its interaction with novel receptors is expected to facilitate apoptosis induction, which could prevent the onset or progression of neurodegenerative diseases and could delay the aging process. Because senescence-associated secreting phenotype determinants are generally inflammatory cytokines or immune factors to activate immune cells. In the central nervous system, C1q has diverse neuroprotective roles against pathogens and inflammation. Most of neurodegenerative diseases show region specific pathology feature in the brain. It has been suggested the evidences that the active site and amount of C1q may be disease specific. This review considers currently the emerging and under-recognized roles of C1q in neurodegeneration and highlights the need for further research to clarify these roles. Future studies on the roles of C1q in regulating disease progression should consider these aspects, including the age-dependent onset time of each neurodegenerative disease progression.

Keywords innate immunity      C1q      aging      neurodegenerative disease      synaptic pruning      neuron      astrocyte      microglia     
Corresponding Authors: Cho Kyoungjoo   
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These authors contributed equally to this study.

Just Accepted Date: 27 January 2019   Issue Date: 28 May 2019
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Kyoungjoo Cho
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Kyoungjoo Cho. Emerging Roles of Complement Protein C1q in Neurodegeneration[J]. Aging and disease, 2019, 10(3): 652-663.
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http://www.aginganddisease.org/EN/10.14336/AD.2019.0118     OR     http://www.aginganddisease.org/EN/Y2019/V10/I3/652
Figure 1.  Structural form and biological functions of C1q

(A) C1q consists of globular heads (gC1q) and a collagen-like region (cC1q). (B) The diagrammatic circle is presenting the functional hallmark of C1q.

Figure 2.  C1q in the CNS aging process

Systemic changes due to aging occur as aged neurons are degenerated by the activation of surveillance microglia. Increased C1q that accompanies aging factors, but not the increased amount itself, may contribute to the aging progression of neurons. CNS-derived C1q is thought to correspond to physiological changes known as senescence-associated secreting phenotype determinants, which are relevant to ROS, DNA damages, and inflammatory cytokines. DAMP, danger-associated molecular pattern; PAMP, pathogen-associated molecular pattern.

Figure 3.  Pathophysiological implications of C1q in neurodegenerative diseases. C1q is involved in the pathological pathway in each neurodegenerative disease due to its role in abnormal protein aggregate clearance, astrocyte reactivation, binding and activation of microglia, or inflammatory responses. C1q in the age-dependent onset time of each neurodegenerative disease participates in regulating disease progression. AD, Alzheimer’s disease; PD, Parkinson’s disease; HD, Huntington’s disease; PrP, prion protein; DC, dendritic cell.
[1] Woodruff TM, Nandakumar KS, Tedesco F (2011). Inhibiting the C5-C5a receptor axis. Mol Immunol, 48:1631-1642.
[2] Sim RB, Laich A (2000). Serine proteases of the complement system. Biochem Soc Trans, 28:545-550.
[3] Reid KBM (2018). Complement Component C1q: Historical Perspective of a Functionally Versatile, and Structurally Unusual, Serum Protein. Front Immunol, 9:764.
[4] Conti P, Shaik-Dasthagirisaheb YB (2015). Mast Cell Serotonin Immunoregulatory Effects Impacting on Neuronal Function: Implications for Neurodegenerative and Psychiatric Disorders. Neurotox Res, 28:147-153.
[5] Nayak A, Ferluga J, Tsolaki AG, Kishore U (2010). The non-classical functions of the classical complement pathway recognition subcomponent C1q. Immunol Lett, 131:139-150.
[6] Cho KJ, Cheon SY, Kim GW (2016). Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q. Sci Rep, 6:18840.
[7] Francis K, van Beek J, Canova C, Neal JW, Gasque P (2003). Innate immunity and brain inflammation: the key role of complement. Expert Rev Mol Med, 5:1-19.
[8] Clarke LE, Liddelow SA, Chakraborty C, Munch AE, Heiman M, Barres BA (2018). Normal aging induces A1-like astrocyte reactivity. Proc Natl Acad Sci U S A, 115:E1896-E1905.
[9] Arlaud GJ, Gaboriaud C, Thielens NM, Rossi V (2002). Structural biology of C1. Biochem Soc Trans, 30:1001-1006.
[10] Presumey J, Bialas AR, Carroll MC (2017). Complement System in Neural Synapse Elimination in Development and Disease. Adv Immunol, 135:53-79.
[11] Rabs U, Martin H, Hitschold T, Golan MD, Heinz HP, Loos M (1986). Isolation and characterization of macrophage-derived C1q and its similarities to serum C1q. Eur J Immunol, 16:1183-1186.
[12] De Bracco MM, Manni JA (1974). Serum levels of C1q, C1r and C1s in normal and pathologic sera. Arthritis Rheum, 17:121-128.
[13] Knobel HR, Villiger W, Isliker H (1975). Chemical analysis and electron microscopy studies of human C1q prepared by different methods. Eur J Immunol, 5:78-82.
[14] Brodsky-Doyle B, Leonard KR, Reid KB (1976). Circular-dichroism and electron-microscopy studies of human subcomponent C1q before and after limited proteolysis by pepsin. Biochem J, 159:279-286.
[15] Kishore U, Ghai R, Greenhough TJ, Shrive AK, Bonifati DM, Gadjeva MG, et al. (2004). Structural and functional anatomy of the globular domain of complement protein C1q. Immunol Lett, 95:113-128.
[16] Gaboriaud C, Teillet F, Gregory LA, Thielens NM, Arlaud GJ (2007). Assembly of C1 and the MBL- and ficolin-MASP complexes: structural insights. Immunobiology, 212:279-288.
[17] Ghebrehiwet B, Hosszu KH, Peerschke EI (2017). C1q as an autocrine and paracrine regulator of cellular functions. Mol Immunol, 84:26-33.
[18] Kishore U, Gaboriaud C, Waters P, Shrive AK, Greenhough TJ, Reid KB, et al. (2004). C1q and tumor necrosis factor superfamily: modularity and versatility. Trends Immunol, 25:551-561.
[19] Heikkinen A, Pihlajaniemi T, Faissner A, Yuzaki M (2014). Neural ECM and synaptogenesis. Prog Brain Res, 214:29-51.
[20] Sim RB, Kishore U, Villiers CL, Marche PN, Mitchell DA (2007). C1q binding and complement activation by prions and amyloids. Immunobiology, 212:355-362.
[21] Kakegawa W, Mitakidis N, Miura E, Abe M, Matsuda K, Takeo YH, et al. (2015). Anterograde C1ql1 signaling is required in order to determine and maintain a single-winner climbing fiber in the mouse cerebellum. Neuron, 85:316-329.
[22] Lei X, Seldin MM, Little HC, Choy N, Klonisch T, Wong GW (2017). C1q/TNF-related protein 6 (CTRP6) links obesity to adipose tissue inflammation and insulin resistance. J Biol Chem, 292:14836-14850.
[23] Gigante A, Gasperini ML, Afeltra A, Barbano B, Margiotta D, Cianci R, et al. (2011). Cytokines expression in SLE nephritis. Eur Rev Med Pharmacol Sci, 15:15-24.
[24] Bordin S, Ghebrehiwet B, Page RC (1990). Participation of C1q and its receptor in adherence of human diploid fibroblast. J Immunol, 145:2520-2526.
[25] Beraudi A, Stea S, Bordini B, Baleani M, Viceconti M (2010). Osteon classification in human fibular shaft by circularly polarized light. Cells Tissues Organs, 191:260-268.
[26] Vegh Z, Kew RR, Gruber BL, Ghebrehiwet B (2006). Chemotaxis of human monocyte-derived dendritic cells to complement component C1q is mediated by the receptors gC1qR and cC1qR. Mol Immunol, 43:1402-1407.
[27] Leigh LE, Ghebrehiwet B, Perera TP, Bird IN, Strong P, Kishore U, et al. (1998). C1q-mediated chemotaxis by human neutrophils: involvement of gClqR and G-protein signalling mechanisms. Biochem J, 330 (Pt 1):247-254.
[28] Hooshmand MJ, Nguyen HX, Piltti KM, Benavente F, Hong S, Flanagan L, et al. (2017). Neutrophils Induce Astroglial Differentiation and Migration of Human Neural Stem Cells via C1q and C3a Synthesis. J Immunol, 199:1069-1085.
[29] Kantrow SP, Shen Z, Jagneaux T, Zhang P, Nelson S (2009). Neutrophil-mediated lung permeability and host defense proteins. Am J Physiol Lung Cell Mol Physiol, 297:L738-745.
[30] Perry VH, O’Connor V (2008). C1q: the perfect complement for a synaptic feast? Nat Rev Neurosci, 9:807-811.
[31] Goodman EB, Anderson DC, Tenner AJ (1995). C1q triggers neutrophil superoxide production by a unique CD18-dependent mechanism. J Leukoc Biol, 58:168-176.
[32] Lood C, Eriksson S, Gullstrand B, Jonsen A, Sturfelt G, Truedsson L, et al. (2012). Increased C1q, C4 and C3 deposition on platelets in patients with systemic lupus erythematosus--a possible link to venous thrombosis? Lupus, 21:1423-1432.
[33] Madhukaran SP, Alhamlan FS, Kale K, Vatish M, Madan T, Kishore U (2016). Role of collectins and complement protein C1q in pregnancy and parturition. Immunobiology, 221:1273-1288.
[34] Xiao J, Li Y, Gressitt KL, He H, Kannan G, Schultz TL, et al. (2016). Cerebral complement C1q activation in chronic Toxoplasma infection. Brain Behav Immun, 58:52-56.
[35] Fonseca MI, Chu SH, Hernandez MX, Fang MJ, Modarresi L, Selvan P, et al. (2017). Cell-specific deletion of C1qa identifies microglia as the dominant source of C1q in mouse brain. J Neuroinflammation, 14:48.
[36] Stephan AH, Madison DV, Mateos JM, Fraser DA, Lovelett EA, Coutellier L, et al. (2013). A dramatic increase of C1q protein in the CNS during normal aging. J Neurosci, 33:13460-13474.
[37] Naviaux JC, Wang L, Li K, Bright AT, Alaynick WA, Williams KR, et al. (2015). Antipurinergic therapy corrects the autism-like features in the Fragile X (Fmr1 knockout) mouse model. Mol Autism, 6:1.
[38] Datwani A, McConnell MJ, Kanold PO, Micheva KD, Busse B, Shamloo M, et al. (2009). Classical MHCI molecules regulate retinogeniculate refinement and limit ocular dominance plasticity. Neuron, 64:463-470.
[39] Ismail FY, Fatemi A, Johnston MV (2017). Cerebral plasticity: Windows of opportunity in the developing brain. Eur J Paediatr Neurol, 21:23-48.
[40] Cherubini E, Caiati MD, Sivakumaran S (2011). In the developing hippocampus kainate receptors control the release of GABA from mossy fiber terminals via a metabotropic type of action. Adv Exp Med Biol, 717:11-26.
[41] Williams PA, Tribble JR, Pepper KW, Cross SD, Morgan BP, Morgan JE, et al. (2016). Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma. Mol Neurodegener, 11:26.
[42] Stephan AH, Barres BA, Stevens B (2012). The complement system: an unexpected role in synaptic pruning during development and disease. Annu Rev Neurosci, 35:369-389.
[43] Lui H, Zhang J, Makinson SR, Cahill MK, Kelley KW, Huang HY, et al. (2016). Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation. Cell, 165:921-935.
[44] Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, et al. (2007). The classical complement cascade mediates CNS synapse elimination. Cell, 131:1164-1178.
[45] Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, et al. (2016). Schizophrenia risk from complex variation of complement component 4. Nature, 530:177-183.
[46] Harry GJ (2013). Microglia during development and aging. Pharmacol Ther, 139:313-326.
[47] Guido W (2008). Refinement of the retinogeniculate pathway. J Physiol, 586:4357-4362.
[48] Hong YK, Chen C (2011). Wiring and rewiring of the retinogeniculate synapse. Curr Opin Neurobiol, 21:228-237.
[49] Katz LC, Shatz CJ (1996). Synaptic activity and the construction of cortical circuits. Science, 274:1133-1138.
[50] Chen C, Regehr WG (2000). Developmental remodeling of the retinogeniculate synapse. Neuron, 28:955-966.
[51] Hooks BM, Chen C (2006). Distinct roles for spontaneous and visual activity in remodeling of the retinogeniculate synapse. Neuron, 52:281-291.
[52] Jaubert-Miazza L, Green E, Lo FS, Bui K, Mills J, Guido W (2005). Structural and functional composition of the developing retinogeniculate pathway in the mouse. Vis Neurosci, 22:661-676.
[53] Torborg CL, Feller MB (2004). Unbiased analysis of bulk axonal segregation patterns. J Neurosci Methods, 135:17-26.
[54] Bialas AR, Stevens B (2013). TGF-beta signaling regulates neuronal C1q expression and developmental synaptic refinement. Nat Neurosci, 16:1773-1782.
[55] McLin VA, Hu CH, Shah R, Jamrich M (2008). Expression of complement components coincides with early patterning and organogenesis in Xenopus laevis. Int J Dev Biol, 52:1123-1133.
[56] Li X, Madison BB, Zacharias W, Kolterud A, States D, Gumucio DL (2007). Deconvoluting the intestine: molecular evidence for a major role of the mesenchyme in the modulation of signaling cross talk. Physiol Genomics, 29:290-301.
[57] Chu Y, Jin X, Parada I, Pesic A, Stevens B, Barres B, et al. (2010). Enhanced synaptic connectivity and epilepsy in C1q knockout mice. Proc Natl Acad Sci U S A, 107:7975-7980.
[58] Ma Y, Ramachandran A, Ford N, Parada I, Prince DA (2013). Remodeling of dendrites and spines in the C1q knockout model of genetic epilepsy. Epilepsia, 54:1232-1239.
[59] Cortes JR, Sanchez-Diaz R, Bovolenta ER, Barreiro O, Lasarte S, Matesanz-Marin A, et al. (2014). Maintenance of immune tolerance by Foxp3+ regulatory T cells requires CD69 expression. J Autoimmun, 55:51-62.
[60] Kannan G, Crawford JA, Yang C, Gressitt KL, Ihenatu C, Krasnova IN, et al. (2016). Anti-NMDA receptor autoantibodies and associated neurobehavioral pathology in mice are dependent on age of first exposure to Toxoplasma gondii. Neurobiol Dis, 91:307-314.
[61] Beglopoulos V, Sun X, Saura CA, Lemere CA, Kim RD, Shen J (2004). Reduced beta-amyloid production and increased inflammatory responses in presenilin conditional knock-out mice. J Biol Chem, 279:46907-46914.
[62] Mallucci GR (2009). Prion neurodegeneration: starts and stops at the synapse. Prion, 3:195-201.
[63] Selkoe DJ (2002). Alzheimer’s disease is a synaptic failure. Science, 298:789-791.
[64] Kouser L, Madhukaran SP, Shastri A, Saraon A, Ferluga J, Al-Mozaini M, et al. (2015). Emerging and Novel Functions of Complement Protein C1q. Front Immunol, 6:317.
[65] Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, et al. (2012). Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron, 74:691-705.
[66] Farber K, Cheung G, Mitchell D, Wallis R, Weihe E, Schwaeble W, et al. (2009). C1q, the recognition subcomponent of the classical pathway of complement, drives microglial activation. J Neurosci Res, 87:644-652.
[67] Lynch NJ, Willis CL, Nolan CC, Roscher S, Fowler MJ, Weihe E, et al. (2004). Microglial activation and increased synthesis of complement component C1q precedes blood-brain barrier dysfunction in rats. Mol Immunol, 40:709-716.
[68] Veerhuis R, Boshuizen RS, Morbin M, Mazzoleni G, Hoozemans JJ, Langedijk JP, et al. (2005). Activation of human microglia by fibrillar prion protein-related peptides is enhanced by amyloid-associated factors SAP and C1q. Neurobiol Dis, 19:273-282.
[69] Fraser DA, Pisalyaput K, Tenner AJ (2010). C1q enhances microglial clearance of apoptotic neurons and neuronal blebs and modulates subsequent inflammatory cytokine production. J Neurochem, 112:733-743.
[70] Rambach G, Maier H, Vago G, Mohsenipour I, Lass-Florl C, Defant A, et al. (2008). Complement induction and complement evasion in patients with cerebral aspergillosis. Microbes Infect, 10:1567-1576.
[71] Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, et al. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 541:481-487.
[72] Lue LF, Rydel R, Brigham EF, Yang LB, Hampel H, Murphy GM, Jr., et al. (2001). Inflammatory repertoire of Alzheimer’s disease and nondemented elderly microglia in vitro. Glia, 35:72-79.
[73] Ingram G, Loveless S, Howell OW, Hakobyan S, Dancey B, Harris CL, et al. (2014). Complement activation in multiple sclerosis plaques: an immunohistochemical analysis. Acta Neuropathol Commun, 2:53.
[74] Thomas A, Gasque P, Vaudry D, Gonzalez B, Fontaine M (2000). Expression of a complete and functional complement system by human neuronal cells in vitro. Int Immunol, 12:1015-1023.
[75] Fan R, Tenner AJ (2004). Complement C1q expression induced by Abeta in rat hippocampal organotypic slice cultures. Exp Neurol, 185:241-253.
[76] Pisalyaput K, Tenner AJ (2008). Complement component C1q inhibits beta-amyloid- and serum amyloid P-induced neurotoxicity via caspase- and calpain-independent mechanisms. J Neurochem, 104:696-707.
[77] Benoit ME, Tenner AJ (2011). Complement protein C1q-mediated neuroprotection is correlated with regulation of neuronal gene and microRNA expression. J Neurosci, 31:3459-3469.
[78] Rupprecht TA, Angele B, Klein M, Heesemann J, Pfister HW, Botto M, et al. (2007). Complement C1q and C3 are critical for the innate immune response to Streptococcus pneumoniae in the central nervous system. J Immunol, 178:1861-1869.
[79] Cai Q, Li Y, Pei G (2017). Polysaccharides from Ganoderma lucidum attenuate microglia-mediated neuroinflammation and modulate microglial phagocytosis and behavioural response. J Neuroinflammation, 14:63.
[80] Mahajan SD, Aalinkeel R, Parikh NU, Jacob A, Cwiklinski K, Sandhu P, et al. (2017). Immunomodulatory Role of Complement Proteins in the Neuropathology Associated with Opiate Abuse and HIV-1 Co-Morbidity. Immunol Invest, 46:816-832.
[81] Whitelaw BS (2018). Microglia-mediated synaptic elimination in neuronal development and disease. J Neurophysiol, 119:1-4.
[82] Moya KL, Benowitz LI, Schneider GE, Allinquant B (1994). The amyloid precursor protein is developmentally regulated and correlated with synaptogenesis. Dev Biol, 161:597-603.
[83] Claasen AM, Guevremont D, Mason-Parker SE, Bourne K, Tate WP, Abraham WC, et al. (2009). Secreted amyloid precursor protein-alpha upregulates synaptic protein synthesis by a protein kinase G-dependent mechanism. Neurosci Lett, 460:92-96.
[84] Kishore U, Gupta SK, Perdikoulis MV, Kojouharova MS, Urban BC, Reid KB (2003). Modular organization of the carboxyl-terminal, globular head region of human C1q A, B, and C chains. J Immunol, 171:812-820.
[85] Nimmrich V, Grimm C, Draguhn A, Barghorn S, Lehmann A, Schoemaker H, et al. (2008). Amyloid beta oligomers (A beta (1-42) globulomer) suppress spontaneous synaptic activity by inhibition of P/Q-type calcium currents. J Neurosci, 28:788-797.
[86] Hirsch E, Graybiel AM, Agid YA (1988). Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson’s disease. Nature, 334:345-348.
[87] Depboylu C, Schafer MK, Arias-Carrion O, Oertel WH, Weihe E, Hoglinger GU (2011). Possible involvement of complement factor C1q in the clearance of extracellular neuromelanin from the substantia nigra in Parkinson disease. J Neuropathol Exp Neurol, 70:125-132.
[88] Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, et al. (2006). In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis, 21:404-412.
[89] Ouchi Y, Yoshikawa E, Sekine Y, Futatsubashi M, Kanno T, Ogusu T, et al. (2005). Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann Neurol, 57:168-175.
[90] Breidert T, Callebert J, Heneka MT, Landreth G, Launay JM, Hirsch EC (2002). Protective action of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone in a mouse model of Parkinson’s disease. J Neurochem, 82:615-624.
[91] Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, et al. (2002). Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci, 22:1763-1771.
[92] Zhang ET, Richards HK, Kida S, Weller RO (1992). Directional and compartmentalised drainage of interstitial fluid and cerebrospinal fluid from the rat brain. Acta Neuropathol, 83:233-239.
[93] Hochmeister S, Zeitelhofer M, Bauer J, Nicolussi EM, Fischer MT, Heinke B, et al. (2008). After injection into the striatum, in vitro-differentiated microglia- and bone marrow-derived dendritic cells can leave the central nervous system via the blood stream. Am J Pathol, 173:1669-1681.
[94] Yamada T, McGeer PL, McGeer EG (1992). Lewy bodies in Parkinson’s disease are recognized by antibodies to complement proteins. Acta Neuropathol, 84:100-104.
[95] Fu H, Hardy J, Duff KE (2018). Selective vulnerability in neurodegenerative diseases. Nat Neurosci, 21:1350-1358.
[96] Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, et al. (1996). Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell, 87:493-506.
[97] Singhrao SK, Neal JW, Morgan BP, Gasque P (1999). Increased complement biosynthesis by microglia and complement activation on neurons in Huntington’s disease. Exp Neurol, 159:362-376.
[98] Ona VO, Li M, Vonsattel JP, Andrews LJ, Khan SQ, Chung WM, et al. (1999). Inhibition of caspase-1 slows disease progression in a mouse model of Huntington’s disease. Nature, 399:263-267.
[99] Bjorkqvist M, Wild EJ, Thiele J, Silvestroni A, Andre R, Lahiri N, et al. (2008). A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington’s disease. J Exp Med, 205:1869-1877.
[100] Dalrymple A, Wild EJ, Joubert R, Sathasivam K, Bjorkqvist M, Petersen A, et al. (2007). Proteomic profiling of plasma in Huntington’s disease reveals neuroinflammatory activation and biomarker candidates. J Proteome Res, 6:2833-2840.
[101] Wild E, Magnusson A, Lahiri N, Krus U, Orth M, Tabrizi SJ, et al. (2011). Abnormal peripheral chemokine profile in Huntington’s disease. PLoS Curr, 3:RRN1231.
[102] Crocker SF, Costain WJ, Robertson HA (2006). DNA microarray analysis of striatal gene expression in symptomatic transgenic Huntington’s mice (R6/2) reveals neuroinflammation and insulin associations. Brain Res, 1088:176-186.
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[15] Dong Liu,Liqun Xu,Xiaoyan Zhang,Changhong Shi,Shubin Qiao,Zhiqiang Ma,Jiansong Yuan. Snapshot: Implications for mTOR in Aging-related Ischemia/Reperfusion Injury[J]. Aging and disease, 2019, 10(1): 116-133.
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